Phenyl urea derivative

Abstract

The present invention relates to a medicament for treating or preventing a disease related to orexin receptor, especially orexin receptor type 2, comprising a new compound having a urea structure or a pharmaceutically acceptable salt thereof as an active ingredient. In more detail, the present invention relates to a medicament for treating or preventing a disease such as narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome.

1 . A compound of formula (1): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, 
       wherein
 R 1  is optionally-substituted C 6-10  aromatic carbocyclyl group, optionally-substituted 5- to 10-membered aromatic heterocyclyl group, optionally-substituted C 3-6  saturated carbocyclyl group, optionally-substituted 4- to 10-membered saturated heterocyclyl group, or cyano; 
 L 1  and L 2  are each independently single bond, methylene (which may be optionally substituted with the same or different one or more C 1-6  alkyl groups), —NR 6 —, —C(═O)—, —OC(═O)—, —SO—, —SO 2 —, —S—, or oxygen atom; 
 R 2  is hydrogen atom, hydroxy group, halogen atom, cyano, optionally-substituted C 1-6  alkyl, optionally-substituted C 1-6  alkoxy, C(═O)NR 3 R 4  or C(═O)O—R 5 ; 
 R 3 , R 4 , R 5  and R 6  are each independently hydrogen atom or optionally-substituted C 1-6  alkyl; 
 ring E is optionally-substituted 5- to 10-membered aromatic heterocyclyl group or optionally-substituted 4- to 10-membered saturated heterocyclyl group; 
 ring G is optionally-substituted C 6-10  aromatic carbocyclyl group, optionally-substituted 5- to 10-membered aromatic heterocyclyl group, optionally-substituted C 3 -6 saturated carbocyclyl group, or optionally-substituted 4- to 10-membered saturated heterocyclyl group; and 
 A is oxygen atom or sulfur atom. 
 
     
     
         2 . The compound according to  claim 1  or a pharmaceutically acceptable salt thereof, wherein in R 2  to R 6 , the optional substituent of “optionally-substituted C 1-6  alkyl” is each independently the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy, or C 3-7  cycloalkyl, and the optional substituent of “optionally-substituted C 1-6  alkoxy” is each independently the same or different one or more substituents selected from halogen atom, hydroxy group, or C 3-7  cycloalkyl,
 in R 1 , the optional substituent of C 6-10  aromatic carbocyclyl group, 5- to 10-membered aromatic heterocyclyl group, C 3-6  saturated carbocyclyl group, and 4- to 10-membered saturated heterocyclyl group is each independently one or more substituents selected from the group consisting of halogen atom, hydroxy group, C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3-7  cycloalkyl), C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3-7  cycloalkyl), C 1-6  alkylamino (the alkyl group of which may be optionally substituted with halogen atom, hydroxy group or C 3-7  cycloalkyl), C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3 —, cycloalkyl), cyano, C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 3-7  cycloalkyl), and 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3-7  cycloalkyl), and 
 in ring E and ring G, the optional substituent of C 6-10  aromatic carbocyclyl group, 5- to 10-membered aromatic heterocyclyl group, C 3-6  saturated carbocyclyl group, and 4- to 10-membered saturated heterocyclyl group is each independently one or more substituents selected from the group consisting of halogen atom, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy or C 3-7  cycloalkyl), C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3-7  cycloalkyl), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 3-7  cycloalkyl), C 1-6  alkylamino (the alkyl group of which may be optionally substituted with halogen atom, hydroxy group or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-6  alkoxy or C 3-7  cycloalkyl), and C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl, C 1-4  alkoxy or C 3-7  cycloalkyl), or when there are plural optional substituents, two of them may be taken together via C 1-6  alkylene to form a chemically-possible bicyclic structure selected from a fused ring, a spiro ring, or bridged ring. 
 
     
     
         3 . The compound according to  claim 1 or 2  or a pharmaceutically acceptable salt thereof, wherein the formula is represented by formula (2): 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is hydroxy group, halogen atom, cyano, optionally-substituted C 1-4  alkyl, optionally-substituted C 1-4  alkoxy, C(═O)NR 3 R 4  or C(═O)OR 5 ; and 
 R 1 , L 1 , L 2 , R 3 , R 4 , R 5 , ring E, ring G, and A are as defined in  claim 1 . 
 
     
     
         4 . The compound according to any one of  claims 1 to 3  or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from cyano or the following formulae (1a-1) to (1a-6): 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  to X 6  are each independently nitrogen atom or CR a4 ; 
 Q 1  and Q 2  are oxygen atom, —NR a5 — or sulfur atom; 
 Q 3  is CH or nitrogen atom; and 
 R a1  to R a5  are each independently (if there are plural CR a4 , each R a4  is also independently) hydrogen atom, halogen atom, C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-4  alkoxy or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl which may be optionally substituted with the same or different one or more halogen atoms, or C 1-6  alkoxy), cyano, C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy), C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), or 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         5 . The compound according to any one of  claims 1 to 4  or a pharmaceutically acceptable salt thereof, wherein ring G is selected from the following formulae (1b-1) to (1b-7): 
       
         
           
           
               
               
           
         
       
       wherein
 W 1  and W 2  are each independently NR b7 , oxygen atom or CR b8 R b9 ; 
 W 3 , W 4 , W 5  and W 6  are each independently nitrogen atom or CR b10 ; 
 R b1  to R b10  are each independently hydrogen atom, halogen atom, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-4  alkoxy), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more halogen atoms), C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), and R b2  and R b3  may bind to the same carbon atom if chemically possible; 
 wherein R b2  and R b3  may be taken together via C 1-6  alkylene to form a fused ring or a bridged ring; and 
 n, m and p are each independently an integer of 1 or 2. 
 
     
     
         6 . The compound according to any one of  claims 1 to 5  or a pharmaceutically acceptable salt thereof, wherein ring E is selected from the following formulae (1c-1) to (1c-4): 
       
         
           
           
               
               
           
         
       
       wherein
 R c1 , R c2 , R c3  and R c4  are each independently hydrogen atom, halogen atom, cyano, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-6  alkoxy), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more halogen atoms), C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), and R c1  and R c2  may bind to the same carbon atom if chemically possible; and 
 wherein R c1  and R c2  may be taken together via C 1-6  alkylene to form a fused ring or a bridged ring. 
 
     
     
         7 . The compound according to any one of  claims 1 to 6  or a pharmaceutically acceptable salt thereof, wherein ring E is selected from the following formulae (1c-11) to (1c-41): 
       
         
           
           
               
               
           
         
       
       wherein
 R c4  is each independently halogen atom, cyano, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-6  alkoxy), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more halogen atoms), C 6-10  aromatic carbocyclyl group (which may be optionally substituted with one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         8 . The compound according to any one of  claims 1 to 7  or a pharmaceutically acceptable salt thereof, wherein the formula is represented by formula (3): 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is C 1-6  alkoxy which may be optionally substituted with halogen atom; and 
 R 1 , A, L 1  and ring G are as defined in  claim 1 . 
 
     
     
         9 . The compound according to any one of  claims 1 to 8  or a pharmaceutically acceptable salt thereof, wherein L 1  is single bond, —CH 2 — or oxygen atom. 
     
     
         10 . The compound according to any one of  claims 1 to 9  or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from the following formulae (1a-1) to (1a-3): 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  to X 5  are each independently nitrogen atom or CR a4 ; 
 Q 1  and Q 2  are each independently oxygen atom or sulfur atom; 
 R a1  is hydrogen atom, halogen atom, cyano, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy), or C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy); and 
 R a4  is each independently (if there are plural CR a4 , each R a4  is independently) hydrogen atom, halogen atom, C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy), C 3-7  cycloalkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), or 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         11 . The compound according to any one of  claims 1 to 10  or a pharmaceutically acceptable salt thereof, wherein ring G is selected from the following formulae (1b-1) to (1b-3): 
       
         
           
           
               
               
           
         
       
       wherein
 R b1  to R b3  are each independently hydrogen atom, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-6  alkoxy), C 1-6  alkoxy (which may be optionally substituted with the same or different one or more halogen atoms), 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         12 . The compound according to any one of  claims 1 to 11  or a pharmaceutically acceptable salt thereof, wherein R 2  is halogen atom selected from F, Cl or Br, and A is oxygen atom. 
     
     
         13 . The compound according to any one of  claims 1 to 12  or a pharmaceutically acceptable salt thereof, wherein R 1  is the following formula (1a-1): 
       
         
           
           
               
               
           
         
       
       wherein
 R a1  is hydrogen atom, halogen atom, cyano, C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy), or C 1-4  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy). 
 
     
     
         14 . The compound according to any one of  claims 1 to 12  or a pharmaceutically acceptable salt thereof, wherein R 1  is the following formula (1a-2): 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  to X 3  are each independently nitrogen atom or CR a4 ; 
 Q 1  is oxygen atom or sulfur atom; 
 R a4  is as defined in  claim 10 ; and
 L 1  is single bond. 
 
 
     
     
         15 . The compound according to any one of  claims 1 to 12  or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from the following formulae (1a-21) to (1a-25): 
       
         
           
           
               
               
           
         
       
       wherein R a4  is as defined in  claim 10 ; and
 L 1  is single bond. 
 
     
     
         16 . The compound according to  claim 15  or a pharmaceutically acceptable salt thereof, wherein R a4  is (if there are plural CR a4 , each R a4  is independently) C 6-10  aromatic carbocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), or 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy). 
     
     
         17 . The compound according to any one of  claims 1 to 12  or a pharmaceutically acceptable salt thereof, wherein R 1  is the following formula (1a-3): 
       
         
           
           
               
               
           
         
       
       wherein X 4  and X 5  are as defined in  claim 10 ; and
 L 1  is single bond. 
 
     
     
         18 . The compound according to  claim 17  or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from the following formulae (1a-31) to (1a-34): 
       
         
           
           
               
               
           
         
       
       wherein R a4  is as defined in  claim 10 . 
     
     
         19 . The compound according to  claim 17 or 18  or a pharmaceutically acceptable salt thereof, wherein R a4  is (if there are plural CR a4 , each R a4  is independently) C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkoxy or C 3-7  cycloalkyl), C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group, C 1-6  alkyl or C 1-6  alkoxy), or C 1-6  alkoxy (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, hydroxy group or C 1-6  alkoxy). 
     
     
         20 . The compound according to any one of  claims 1 to 19  or a pharmaceutically acceptable salt thereof, wherein ring G is the following formula (1b-2): 
       
         
           
           
               
               
           
         
       
       wherein R b2  is as defined in  claim 11 . 
     
     
         21 . The compound according to any one of  claims 1 to 19  or a pharmaceutically acceptable salt thereof, wherein ring G is the following formula (1b-1): 
       
         
           
           
               
               
           
         
       
       wherein
 R b1  is C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-6  alkoxy), 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         22 . The compound according to any one of Items 1 to 19 or a pharmaceutically acceptable salt thereof, wherein ring G is the following formula (1b-3): 
       
         
           
           
               
               
           
         
       
       wherein
 R b3  is C 1-6  alkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom or C 1-6  alkoxy, 5- to 10-membered aromatic heterocyclyl group (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy), or C 3-7  cycloalkyl (which may be optionally substituted with the same or different one or more substituents selected from halogen atom, C 1-6  alkyl or C 1-6  alkoxy). 
 
     
     
         23 . The compound according to  claim 1  or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following compounds:
 N-{2-fluoro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methyl-4-[5-(propan-2-yl)-1,2,4-oxadiazol-3-yl]piperidine-1-carboxamide 
 N-{2-fluoro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)piperidine-1-carboxamide 
 4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-N-{2-fluoro-6-[1-(propan-2-yl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-4-methylpiperidine-1-carboxamide 
 4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-N-{2-fluoro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methylpiperidine-1-carboxamide 
 4-(5-cyclopropyl-1,2-oxazol-3-yl)-N-{2-fluoro-6-[1-(propan-2-yl)piperidin-4-yl]phenyl}-4-methylpiperidine-1-carboxamide 
 4-(5-cyclopropyl-1,2-oxazol-3-yl)-N-{2-fluoro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methylpiperidine-1-carboxamide 
 4-(5-cyclopropyl-1,2-oxazol-3-yl)-N-{2-fluoro-6-[1-(propan-2-yl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-(5-cyclopropyl-1,2-oxazol-3-yl)-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methyl-4-(4-methylphenyl)piperidine-1-carboxamide. 
 
     
     
         24 . The compound according to  claim 1  or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the following compounds:
 4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-ethyl-N-{2-fluoro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}piperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-ethylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-(5-cyclopropyl-1,3-thiazol-2-yl)-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-{5-[(1S,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-{5-[(1R,2R)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methyl-4-{5-[(1S,2R)-2-methylcyclopropyl]-1,2,4-oxadiazol-3-yl}piperidine-1-carboxamide 
 N-{2-chloro-6-[4-(propan-2-yl)piperazin-1-yl]phenyl}-4-methyl-4-{5-[(1R,2S)-2-methylcyclopropyl]-1,2,4-oxadiazol-3-yl}piperidine-1-carboxamide 
 N-{2-chloro-6-[1-(propan-2-yl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-4-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[1-(propan-2-yl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-4-(5-cyclopropyl-1,2-oxazol-3-yl)-4-methylpiperidine-1-carboxamide 
 N-{2-chloro-6-[1-(propan-2-yl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-4-methyl-4-(4-methylphenyl)piperidine-1-carboxamide. 
 
     
     
         25 . A pharmaceutical composition comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         26 . A medicament for treating a disease associated with orexin receptor type 2, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         27 . A medicament for treating narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome involving narcolepsy-like symptom, hypersomnia associated with Parkinson's disease, hypersomnia associated with dementia with Lewy body, hypersomnia syndrome involving daytime hypersomnia (for example, Kleine-Levin syndrome, major depression accompanied by hypersomnia, dementia with Lewy body, Parkinson's disease, progressive supranuclear palsy, Prader-Willi syndrome, Moebius syndrome, hypoventilation syndrome, Niemann-Pick disease type C, brain contusion, cerebral infarction, brain tumor, muscular dystrophy, multiple sclerosis, acute disseminated encephalomyelitis, Guillain-Barre syndrome, Rasmussen's encephalitis, Wernicke's encephalopathy, limbic encephalitis, Hashimoto encephalopathy), coma, loss of consciousness, obesity (for example, malignant mast cell, extrinsic obesity, hyperinsulinar obesity, hyperplasmic obesity, hypophysial obesity, hypoplasmic obesity, hypothyroid obesity, hypothalamic obesity, symptomatic obesity, childhood obesity, upper body obesity, alimentary obesity, gonadal obesity, systemic mastocytosis, primary obesity, central obesity), insulin resistance syndrome, Alzheimer, impaired consciousness such as coma, side effect or complication caused by anesthesia, sleep disturbance, sleep problem, insomnia, intermittent sleep, night myoclonus, REM sleep interruption, jet lag, jet lag syndrome, sleep disorder of shift workers, dyssomnia, sleep terror, depression, major depression, sleepwalking, enuresis, sleep disorder, Alzheimer's sundown syndrome, disease associated with circadian rhythm, fibromyalgia, condition resulting from decrease in sleeping quality, bulimia, obsessive eating disorder, obesity-related diseases, hypertension, diabetes, elevated plasma insulin level/insulin resistance, hyperlipemia, hyperlipidaemia, endometrial cancer, breast cancer, prostate cancer, colon cancer, cancer, osteoarthritis, obstructive sleep apnea, cholelithiasis, gallstone, heart disease, abnormal heartbeat, arrhythmia, myocardial infarction, congestive heart failure, coronary heart disease, cardiovascular disease, sudden death, polycystic ovary, craniopharyngioma, Prader-Willi syndrome, Froehlich syndrome, growth hormone deficiency, normal variant short stature, Turner syndrome, children suffering from acute lymphoblastic leukemia, syndrome X, reproductive hormone abnormality, decrease of fecundability, infertility, hypogonadism in men, sexual/reproductive-function dysfunction such as hirsutism in women, fetal defect associated with maternity obesity, gastrointestinal motility disorder such as obesity-related gastroesophageal reflux, obesity hypoventilation syndrome (Pickwickian syndrome), respiratory disease such as respiratory distress, inflammation such as vascular systemic inflammation, arteriosclerosis, hypercholesterolemia, hyperuricemia, low back pain, gallbladder disease, gout, renal cancer, secondary risk of obesity such as risk of left ventricle hypertrophy, migraine, headache, neuropathic pain, Parkinson's disease, psychosis, schizophrenia, facial flushing, night sweat, disease in  genitalium /urinary system, disease associated with sexual function or fecundability, dysthymic disorder, bipolar disorder, bipolar I disorder, bipolar II disorder, cyclothymic disorder, acute stress disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic attack, panic disorder, posttraumatic stress disorder, separation anxiety disorder, social phobia, anxiety disorder, acute neurological and psychiatric disorder such as cerebral deficiency developed after heart bypass surgery or heart transplant, stroke, ischemic stroke, cerebral ischemia, spinal cord trauma, head injury, periparturient hypoxia, cardiac arrest, hypoglycemic nerve injury, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, eye damage, retinopathy, cognitive impairment, muscle spasm, tremor, epilepsy, disorder associated with muscle spasm, delirium, amnestic disorder, age-associated cognitive decline, schizoaffective disorder, paranoia, drug addiction, movement disorder, chronic fatigue syndrome, fatigue, medication-induced parkinsonian syndrome, Gilles de la Tourette syndrome, chorea, myoclonus, tic, restless legs syndrome, dystonia, dyskinesia, attention deficit hyperactivity disorder (ADHD), conduct disorder, urinary incontinence, withdrawal symptom, trigeminal neuralgia, hearing loss, tinnitus, nerve injury, retinopathy, macular degeneration, vomiting, cerebral edema, pain, bone pain, arthralgia, toothache, cataplexy, or traumatic brain injury, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         28 . A medicament for treating narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome involving narcolepsy-like symptom, hypersomnia associated with Parkinson's disease, or hypersomnia associated with dementia with Lewy body, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         29 . A medicament for treating narcolepsy, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         30 . A medicament for treating idiopathic hypersomnia, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         31 . A medicament for treating hypersomnia associated with Parkinson's disease, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         32 . A medicament for treating hypersomnia associated with dementia with Lewy body, comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof. 
     
     
         33 . A method of treating narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome involving narcolepsy-like symptom, hypersomnia associated with Parkinson's disease, or hypersomnia associated with dementia with Lewy body, which comprises administering a therapeutically effective amount of the compound of any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof to a patient in need thereof. 
     
     
         34 . Use of the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome involving narcolepsy-like symptom, hypersomnia associated with Parkinson's disease, or hypersomnia associated with dementia with Lewy body. 
     
     
         35 . A pharmaceutical composition comprising the compound according to any one of  claims 1 to 24  or a pharmaceutically acceptable salt thereof for use in the treatment of narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, narcolepsy syndrome involving narcolepsy-like symptom, hypersomnia associated with Parkinson's disease, or hypersomnia associated with dementia with Lewy body.